Dissecting Chromosome Segregation

During cell division, the centromere regions of chromosomes assemble multiprotein organelles called kinetochores that form attachments to spindle microtubules. Working in Caenorhabditis elegans, Cheerambathur et al. (p. 1239, published online 14 November) describe a mechanism controlling the formation of kinetochore-spindle microtubule attachments that is essential for accurate chromosome segregation. The findings suggest the existence of crosstalk between the two major protein complexes involved in forming spindle microtubule attachments: the kinetochore dynein module, which initially captures spindle microtubules, and the Ndc80 complex, which ultimately forms the dynamic end-coupled attachments that segregate chromosomes.

Abstract

The microtubule-based mitotic spindle segregates chromosomes during cell division. During chromosome segregation, the centromeric regions of chromosomes build kinetochores that establish end-coupled attachments to spindle microtubules. Here, we used the Caenorhabditis elegans embryo as a model system to examine the crosstalk between two kinetochore protein complexes implicated in temporally distinct stages of attachment formation. The kinetochore dynein module, which mediates initial lateral microtubule capture, inhibited microtubule binding by the Ndc80 complex, which ultimately forms the end-coupled attachments that segregate chromosomes. The kinetochore dynein module directly regulated Ndc80, independently of phosphorylation by Aurora B kinase, and this regulation was required for accurate segregation. Thus, the conversion from initial dynein-mediated, lateral attachments to correctly oriented, Ndc80-mediated end-coupled attachments is actively controlled.